Enzymes are a class of important substances and their abnormal levels are associated with many diseases. Great progress has been achieved in the past decade in the detection and imaging of enzymes in live cells and tissues. Small-molecule fluorescent probes have the ability to directly detect and image abnormal levels of enzymes in live cells, providing a powerful means for diagnostics and treatment. Combined with confocal microscopy, fluorescent probes have attracted much attention because of their high sensitivity and spatiotemporal resolution. Tyrosinase is a copper-containing oxidase that plays a key role in the biosynthesis of melanin that controls skin color, protects DNA in skin cells from ultraviolet radiation, and removes reactive oxygen species. An abnormal level of tyrosinase in living system is thought to be associated with some skin diseases including albinism, vitiligo and skin hyperpigmentation. Overexpressed tyrosinase has become a predictive biomarker for melanoma cancer, which makes in situ the detection of endogenous tyrosinase activity of great value and clinical significance. This review highlights the recent development of organic small-molecules based fluorescent probes for endogenous tyrosinase activity, including design strategies, reaction mechanism and applications for the detection and imaging of tyrosinase in vitro and in vivo. The progress suggests that fluorescence detection and imaging is a vital and rapidly technology for early diagnosis of melanoma.